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Nanotechnology in the Clinical Laboratory
Jeannette P. Caruso, MHP, Drexel University College of Medicine
Introduction:
Nanotechnology is a multidisciplinary scientific field of study that encompasses a vast
array of technologies derived from engineering, physics, biology and chemistry. The advances
in nanotechnology over the years in the electronics industry, for instance, have allowed for
progressively smaller devices with greater complexity and memory. We are now beginning to
see a promising future of nanotechnology in medicine and the clinical laboratory using devices
and reagents on the nanometer scale that will hopefully mirror its success in other industries.
Currently, there has been success using nanotechnology in the clinical laboratory. Most
significantly, is the use of quantum dots (QDs) in flow cytometry. Quantum dots (QDs) have
also shown great success in immunohistochemistry applications, as well. The future of
nanotechnology in medicine and the clinical laboratory offers many possibilities and may
completely change the current methods of laboratory diagnostics.
Nanoparticles can also be used as scaffolds for enzyme labels. Traditionally in
immunohistochemistry, one antibody is coupled with one to several dye labels. Quantum dots,
given
their larger size, can be couple
A
B with a number of antibodies. Fluorescent in situ
hybridization (FISH) has adopted the use of oligonucleotide conjugated QDs which have
proven to be significantly brighter and have more photostable signals than traditional organic
dyes. This allows for more stable and quantitative uses of FISH (Cai, Hsu and Li).
Since no single modality is perfect and sufficient to obtain all necessary information, one
of the most promising uses of nanotechnology in the near future is the development of
multifunctional QD-based probes for multimodality imaging both in vitro and in vivo (Cai,
Hsu and Li). Imaging would include the use of positron emission tomography (PET), magnetic
resonance imaging (MRI), and single photon emission computed tomography (SPECT). This
would make it possible to image targeted QDs from the whole body down to the nanometer
scale using a single probe.
.
Background:
The concept of nanotechnology is not new. In fact, the concept of nanotechnology was
first introduced in the 1950’s by a physicist, Richard Feynman. Although the concept was first
introduced 1950’s, the actual term “nanotechnology” was not coined until the mid 1970’s by a
researcher, Norio Taniguchi. Initially, the electronics industry was the primary driving force in
nanotechnology research, which endeavored to create smaller, faster and more complex devices.
Surprisingly, it’s only been in the last 10 years or so, through public and private funding,
that a real emphasis has been placed on nanotechnology in many different fields, including
medicine. In addition to private and public funding, the U.S. government also funds billions of
dollars to the National Nanotechnology Initiative to encourage research and development in
nanotechnology in a variety of disciplines. The National Science Foundation has predicted the
impact of advances emerging from nanotechnology developments over the next 20 years to be
approximately $1 trillion and in anticipation of this economic impact the number of
nanotechnology research programs has increased substantially (Sahoo 2007). The rapid
advances in science and technology have opened the door for nanotechnology and promises
new opportunities on the horizon for disease treatment and diagnosis in health care.
Current Use of Nanotechnology in the Clinical Laboratory:
Currently, quantum dots are a type of nanotechnology being used in the flow cytometry
laboratory. Quantum dots (QDs) are inorganic nanocrystals with unique properties that provide
fluorescent labels. Flow cytometry analyzes complex antigen distributions on cell populations
by applying fluorescent antibody conjugates to quantify antigen marker expression on cells,
one color per marker (Buller, Zhang and Godfrey). Typically, organic dyes are used but are
being outperformed by quantum dots in many ways. Compared to organic dyes, QDs have
narrow emissions that require much less spectral compensation, more resistant to
photobleaching, continuous absorption spectra from UV to near-infrared (NIR), longer
fluorescence lifetime, and large Stokes shifts. Additionally, a single excitation source can be
used to simultaneously visualize multiple QDs with different emission spectra (Cai, Hsu and
Li). Over the last ten years, QDs have overcome many of the limitations of traditional organic
dyes.
Figure 2 | Schematics of a QD-antibody conjugate and a dye-labeled antibody, reflecting the proportions of the
components. (Resch-Genger, Grabolle and Cavaliere-Jaricot)
Future of Nanotechnology in the Clinical Laboratory:
Applications of nanotechnology in the future laboratory will be developed that
completely replace current laboratory diagnostic methods. Hopes are high that in vivo imaging
diagnostics methods are on the horizon which could potentially reduce or even replace current
methods of biopsies and tissue processing. There are still many areas that still need to be
resolved before nanoparticles (i.e. QDs) can become completely effective in vivo. The first
issue is to be able to accurately direct nanoparticles to a specific organ or diseased tissue site
without alteration. The size of the nanoparticle is another issue (QDs are approximately 20
nm). For example, being able to pass through pores and gain access to areas such as the
nucleus. In vivo imaging has been successful in mice, but has not been accomplished in larger
species, such as humans due to a short circulation time. Additionally, little is known about the
toxicity of nanoparticles, especially since molecules on this scale behave differently. With
continued research and demand for nanotechnology, the future of in vivo diagnostics in human
health care is promising.
Figure 4. Dualfunctional Qdbased probe for both PET and NIRF imaging. (a) PET image of harvested
major organs/tissues at 5 h post-injection of the dualfunctional probe. (b) NIRF image of harvested major
organs/tissues at 5 h post-injection of the probe. (c) Immunofluorescence staining of the tumor tissue
revealed that QDs are targeting the tumor vasculature. (Cai, Hsu and Li)
Conclusion:
Nanotechnology has the potential to significantly impact disease diagnosis and patient
disease management, as well as the methods used in the clinical laboratory. It is anticipated that
nanotechnology will continue to evolve and be implemented in many areas of medical sciences
and patient treatment as we have already seen with the use of quantum dots. Although there is
still much to learn and many challenges overcome the future development and implementation
of nanotechnology in medicine and the clinical laboratory are on the horizon.
References:
Barteneva, N. and I. Vorobjev. "Quantum dots in microscopy and cytometry: immunostaing applications." Microscopy: Science, Technology,
Application and Education (2010): 710-721.
Buller, Gayle M., Yu-Zhong Zhang and William L. Godfrey. Quantum Dots as Replacements for Tandem Dyes in Flow Cytometry. Scientific. Eugene,
OR: Invitrogen Corporation, 2008.
Cai, Weibo, et al. "Are quantum dots ready for in vivo imaging in human subjects? ." Nanoscale Res Lett (2007): 265-281.
Figure 1 | Spectra of QDs and organic dyes
(a–f) Absorption (lines) and emission
(symbols) spectra of representative QDs (a–c)
and organic dyes (d–f) color coded by size
(blue < green < black < red). MegaStokes
dyes were designed for spectral multiplexing
in dimethylformamide (DMF). (ReschGenger, Grabolle and Cavaliere-Jaricot)
Park, Jason Y. "Nanotechnology in the Clinical Laboratory." Critical Values: News for the Entire Laboratory Team (2008): 9-11.
Resch-Genger, Ute, et al. "Quantum Dots Versus Organic Dyes as Fluorescent Labels." Nature Methods (2008): 763-775.
Sahoo, S. K., S. Parveen and J. J. Panda. "The Present and Future of Nanotechnology in Human Health Care." Nanomedicine: Nanotechnology,
Biology, and Medicine (2007): 20-31.
Dimitrios Kirmizis, Fani Chatzopoulou, Eleni Gavriilaki and Dimitrios Chatzidimitriou (2012). Applications of Quantum Dots in Flow Cytometry,
Flow Cytometry - Recent Perspectives, M.Sc. Ingrid Schmid (Ed.), ISBN: 978-953-51-0626-5, InTech, DOI: 10.5772/39065. Available from:
http://www.intechopen.com/books/flow-cytometry-recent-perspectives/applications-of-quantum-dots-in-flow-cytometry
Figure 3 Antibody-conjugated QDs for in vivo cancer targeting and imaging. Mouse on the left was a control
(Cai, Hsu and Li).